Most medical drug treatments have utilized a reductionist approach: one molecule for one cellular pathophysiological condition. Although the reductionist approach has proven successful for monogenic diseases, it has failed for complex diseases. Physicians have recognized that a combination of approaches is required to treat complex disorders such as type 1 or type 2 diabetes. One treatment for diabetes is the administration of insulin injections, which dates back to 1922. However, insulin injections do not stop the development of diabetic complications (e.g., retinopathy, neuropathy, nephropathy, cardiovascular disease, and stroke) in many type 1 and type 2 diabetic patients. The treatment cost of these diabetic complications is enormous and contributes in a major way to the increased cost health care in diabetic patients.
Although advances have been made in biomedical research, scientists and clinicians are still looking for effective treatments for diabetes. In certain forms of diabetes beta cells are damaged, deficient, or depleted. Potential treatments for diabetes include drug-based therapies and cell-based therapies, both of which have their limitations. Drug-based therapies usually treat symptoms only and patients are chronically dependent on them. Cell-based therapies are hampered by the scarcity of cells and their source, immune rejection, and high manufacturing and distribution costs.
Cell-based therapy is one approach to the treatment of diabetes and other conditions in which a reduction in pancreatic beta cell number or beta cell function is causative or contributory (D'Amour et al., Nature Biotech 24:1392-1401, 2006; Kroon et al., Nature Biotech 26:443-452, 2008). Multicomponent cocktails is one method for reproducing embryonic precursors of beta cells, for example a cocktail of transcriptional factors has been used in stem cell research (Eminli et al., Nature Genetics 41:968-976, 2009) or a viral vector cocktail has been used more recently in the mouse (Zhou et al., Nature 455: 627-632, 2008). In general these cells are not fully developed in their response to glucose, and although the cells contain and express insulin, they fail to secrete insulin in the presence of glucose or in response to changes in glucose concentration.
Thus, there remains a need for methods of treating diabetes, such as producing beta cells that express and secret insulin in vivo in a subject.